Dydrogesterone disrupts lipid metabolism in zebrafish brain: A study based on metabolomics and Fourier transform infrared spectroscopy. (15th January 2023)

• Record Type: Journal Article
• Authors: Jiang, Yu-Xia; Shi, Wen-Jun; Hu, Li-Xin; Ma, Dong-Dong; Zhang, Hui; Ong, Choon Nam; Ying, Guang-Guo
• Is Part Of: Environmental pollution. Volume 317(2023)
• Publication Date: 2023-01-15
• Subjects: Dydrogesterone -- Zebrafish -- Brain -- Metabolomics -- FTIR -- Lipid metabolism; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2022.120811
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: Brain is a potential target for neuroprogestogens and/or peripheral progestogens. Previous studies reported that expression of genes about steroidogenesis, reproduction, cell cycle, and circadian rhythm in zebrafish brain could be affected by progestogens. However, there are limited information from metabolites or biomacromolecules aspects, leaving an enormous gap in understanding toxic effects of progestogens on fish brain. In this study, we exposed zebrafish embryos to 2.8, 27.6, and 289.8 ng/L dydrogesterone (DDG, a synthetic progestogen) until sexual maturity (140 days). LC-MS and GC-MS based untargeted metabolomics and Fourier-transform infrared (FTIR) spectroscopy were then performed to investigate the metabolic profiles and macromolecular changes of brain of these zebrafish. The results from multivariate statistical analysis of metabolite features showed a clear separation between different treatment groups of both female and male zebrafish brains. DDG exposure increased the levels of cholesterol, saturated fatty acids, and nucleoside monophosphates, but decreased the contents of polyunsaturated fatty acids (PUFAs), lysophosphatides, and nucleosides in dose-dependent manner. FTIR results indicated that DDG exposure led to accumulation of saturated lipids, reduction of nucleic acids and carbohydrates, and alteration of protein secondary structures. The findings from this study demonstrated that DDG could affect contents of metabolites and biomacromolecules of zebrafish brain, which may finally lead to brain dysfunctions. Graphical abstract: Image 1 Highlights: DDG increased levels of cholesterol and nucleoside monophosphates. DDG decreased contents of polyunsaturated fatty acids. DDG led to accumulation of saturated lipids. Metabolic profile closely correlated to transcriptional alteration of circadian clock.